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Clinical Trials/NCT05665465
NCT05665465RecruitingEarly Phase 1

Neurobehavioral Mechanisms Linking Childhood Adversity to Increased Risk for Smoking

Duke University1 site in 1 country150 target enrollmentStarted: January 19, 2024Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Early Phase 1
Status
Recruiting
Enrollment
150
Locations
1
Primary Endpoint
Subjective effects of nicotine nasal spray as measured by the Nicotine Effects Questionnaire

Study Overview

Brief Summary

The purpose of this study is to evaluate how certain childhood experiences influences brain function and responses to nicotine exposure in a group of nonsmoking young adults. The investigators assess responses to nicotine exposure by giving participants a small amount of nicotine or placebo, and then asking them to answer questionnaires. The investigational drugs used in this study are a nicotine nasal spray (i.e., Nicotrol) and/or a nasal spray placebo (made of common kitchen ingredients, including a very tiny amount of pepper extract also called capsaicin). The investigators assess brain function through function magnetic resonance imaging (fMRI), which is a noninvasive procedure that uses a magnetic field to take pictures of your brain while you are performing certain tasks. This study will help us to learn more about why some childhood experiences (adverse childhood experiences, or ACEs) contribute to increased risk for smoking and other substance use.

Detailed Description

Individuals with a history of adverse childhood experiences (ACEs) are more likely to smoke cigarettes than those without, but little is known about the factors that account for this increased risk. This study will examine brain function in regions related to reward processing and inhibitory control, along with reactions to initial nicotine exposure to help explain why ACEs lead to increased risk for smoking. In this study, young adult non-smokers ages 18-21 (n=150) with a history of exposure to ACEs ranging from 0 to 4 or more will be enrolled to attend 7 visits including an MRI scan and administration of a nicotine nasal spray. Participants will complete an in-person screening visit, followed by a training visit to provide training for the MRI tasks and to acclimate them to the mock MRI scanner. They will then complete a functional neuroimaging scanning session to examine brain reactivity during a monetary reward task, an inhibitory control task, and during rest. Participants will then attend 3 separate visits in which subjective reactions to a nasal spray containing 0, .5, or 1 mg doses of nicotine will be measured. During a final choice session participants will choose to self-administer nicotine or placebo nasal spray. Breath and urine samples will be collected at each visit to test for recent smoking, alcohol use, or illicit drug use. Plasma samples will be collected at each fixed-dose session to assess nicotine and cotinine levels. All nicotine administration will occur during laboratory sessions, and the study physician will be on site or on call during all visits.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)

Eligibility Criteria

Ages
18 Years to 21 Years (Adult)
Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • generally healthy
  • 18-21 years of age
  • never smoked a full cigarette or used an equivalent amount of other nicotine or tobacco products
  • no tobacco exposure in the past 3 years
  • expired air CO level ≤ 3 ppm
  • corroboration of non-smoking status from 2 collateral reporters
  • breath alcohol value = 0.000

Exclusion Criteria

  • use of illegal drugs as measured by urine drug screen
  • reported history of illicit drug use > 10 times lifetime
  • lifetime history of alcohol use disorder
  • binge drinking > 5 times per month over the past 3 months
  • history of serious mental illness including bipolar or psychotic disorders
  • significant medical or unstable psychiatric disorders
  • systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg
  • heart rate ≥ 100 bpm
  • use of psychoactive medications (e.g., antidepressants, opioid analgesics, etc.) in the past 6 months
  • presence of conditions that would make fMRI unsafe (e.g., pacemaker)
  • brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder)
  • history of serious traumatic brain injury
  • claustrophobia
  • lack of firm resolve to refrain from cigarette, e-cigarette or other tobacco use in the coming year
  • pregnant, trying to become pregnant, or breastfeeding
  • inability to understand written and/or spoken English language
  • inability to attend all experimental sessions

Arms & Interventions

Placebo

Placebo Comparator

Participants will be administered 2 nasal sprays with a combined nicotine content of 0mg nicotine, 0.1mL

Intervention: Placebo (Drug)

0.5mg nicotine

Experimental

Participants will be administered 2 nasal sprays with a combined nicotine content of 0.5 mg nicotine, 0.1mL

Intervention: Nicotine nasal spray 0.5 mg (Drug)

0.5mg nicotine

Experimental

Participants will be administered 2 nasal sprays with a combined nicotine content of 0.5 mg nicotine, 0.1mL

Intervention: Placebo (Drug)

1mg nicotine

Experimental

Participants will be administered 2 nasal sprays with a combined nicotine content of 1.0 mg nicotine, 0.1mL

Intervention: Nicotine nasal spray 0.5 mg (Drug)

Outcomes

Primary Outcomes

Subjective effects of nicotine nasal spray as measured by the Nicotine Effects Questionnaire

Time Frame: during fixed dose session, approximately 3 hrs

subjective effects will be measured by the Nicotine Effects Questionnaire at the end of each fixed dose session. This scale measure positive reactions, negative reactions, and dizziness on a scale from 0-3 where 0 is none and 3 is intense.

Subjective effects of nicotine nasal spray as measured by a visual analog scale

Time Frame: during fixed dose session, approximately 3 hrs

subjective effects will be measured on a visual analog scale at the end of each fixed dose session. Ratings will be provided on a scale of 0=not at all to 100=an awful lot.

Reinforcing effects of nicotine nasal spray

Time Frame: during choice session, approximately 4 hrs

reinforcing effects will be measured by the number of choices for nicotine spray (range 0-8) during the forced choice session.

Percent BOLD signal change in ventral striatum

Time Frame: baseline, prior to intervention

Percent blood oxygen level-dependent (BOLD) signal change during anticipation of monetary gain versus baseline during the Reward Guessing Task will be extracted from the bilateral ventral striatum

Percent BOLD signal change in inferior frontal gyrus

Time Frame: baseline, prior to intervention

Percent BOLD signal change during "rare go" versus "no-go" trials during the Go/No-Go Task will be extracted from the right inferior frontal gyrus

Secondary Outcomes

No secondary outcomes reported

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (1)

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